Questions remain about the benefits of taking testosterone

As a treatment for the ailments of aging, testosterone’s benefits are hit or miss.

For men with low testosterone, the hormone therapy is helpful for some health problems, but not so much for others, researchers report in five papers published February 21 in JAMA and JAMA Internal Medicine. Testosterone therapy was good for the bones, but didn’t help memory. It remedied anemia and was linked to a lower risk of heart attack and stroke. But treatment also upped the amount of plaque in the arteries, an early indicator of heart attack risk, researchers report.

“It’s a very confusing area,” says Caleb Alexander, a prescription drug researcher at Johns Hopkins Bloomberg School of Public Health, who was not involved with the work. “Testosterone very well may help men feel more energized,” he says. “But the real question is: At what cost?”

As men age, their testosterone levels tend to drop. Researchers have suggested that boosting the levels back up to normal might counter some signs of aging, including memory loss and weakened bones. But the risks of such treatment — especially the cardiovascular risks — remain unclear, Alexander says. Dozens of studies have tackled the question, but the results “point in lots of different directions,” he says.

Despite lack of clarity on testosterone therapy’s safety and benefits, the number of men taking the hormone has soared in recent years. One 2014 analysis estimated that 2.2 million men filled testosterone prescriptions in 2013 compared with 1.2 million men in 2010. That includes many men with testosterone levels on the borderline between low and normal, men who don’t actually meet clinical guidelines for treatment, Alexander says.

The new studies attempted to answer some of the long-standing questions about the pros and cons of treatment. Four present findings from a set of clinical trials known as the Testosterone Trials, designed to evaluate the effects of testosterone therapy in men age 65 or older.

One study found that the density and strength of hip and especially spine bones improved after a year of using a daily dose of testosterone gel. Researchers don’t yet know whether these gains will translate to fewer fractures. Daily testosterone gel treatment over a year also helped men recover from anemia, raising levels of hemoglobin, an oxygen-carrying molecule in the blood, a second study showed. But testosterone gel didn’t seem to have an effect on men’s memory and cognition. In a study of 788 men, those who took the hormone performed about as well on memory and other tests as those who got a placebo.

Two studies attempted to untangle how exactly testosterone treatment affects the heart and blood vessels. One study, part of the Testosterone Trials, linked testosterone treatment with more plaque buildup in the vessels that carry oxygen-rich blood to the heart. That sounds ominous. Too much plaque can block blood flow and cripple the heart. But the second study didn’t find more heart attacks, strokes or other cardiovascular problems in men taking the hormone. In that study, researchers examined medical records of more than 44,000 men, around 8,800 of whom had been given a prescription for testosterone treatment. Over a roughly three-year follow-up period, these men actually had a lower risk of cardiovascular issues than men who hadn’t been given a testosterone prescription, researchers report.

The new work does “little overall to clarify the role of testosterone replacement” for cardiovascular risk and cognitive function, says Dimitri Cassimatis, a cardiologist at Emory University School of Medicine in Atlanta. But taken together, he says, the studies strengthen the evidence for testosterone’s benefits on bone density and anemia.